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accession-icon SRP070439
Multivalent binding of PWWP2A to H2A.Z-marked transcriptional active chromatin regulates mitosis and organ development [RNA-seq]
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 1500

Description

The essential histone variant H2A.Z affects various DNA-based biological processes by so far not well understood mechanisms. Using a comprehensive label-free quantitative mass spectrometry-based approach we identified the human H2A.Z nucleosome interactome providing further insights into H2A.Z’s regulatory functions. Besides histone modification writer, eraser and reader complexes we identified PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A binds unprecedented strong to chromatin through a concerted multivalent binding mode. Two internal protein regions separately allow H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain mediates direct DNA binding. PWWP2A is found at euchromatic regions where it preferable binds to the H2A.Z-nucleosome-containing transcriptional start sites of transcribed genes. Cellular depletion of PWWP2A results in impaired proliferation caused by a mitotic delay likely due to deregulation of involved target genes. According with the strong cellular phenotype, knockdown of frog PWWP2A leads to severe developmental cranial facial defects arising from neural crest cell differentiation and migration problems. Together, this study identifies PWWP2A as an H2A.Z-specific multivalent chromatin binder and provides a novel link between H2A.Z, chromosome segregation and organ development. Overall design: RNASeq of HeLa cells treated with control or PWWP siRNA

Publication Title

Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation.

Alternate Accession IDs

GSE78003

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP022043
A blood based 12-miRNA signature of Alzheimer patients
  • organism-icon Homo sapiens
  • sample-icon 70 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

We applied Next-Generation Sequencing (NGS) to miRNAs from blood samples of 48 AD (Alzheimer''s Disease) patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression level. Of these, 82 were higher and 58 lower abundant in samples from AD patients. We selected a panel of 12 miRNAs for a qRT-PCR analysis on a larger cohort of 202 samples including not only AD patients and healthy controls but also patients with other CNS illnesses: Multiple Sclerosis, Parkinson''s Disease, Major Depression, Bipolar Disorder, Schizophrenia, and Mild Cognitive Impairment, which is assumed to represent a transitional period before the development of AD. MiRNA target enrichment analysis of the selected 12 miRNAs indicated an involvement of miRNAs in nervous system development, neuron projection, neuron projection development, and neuron projection morphogenesis, respectively. Using this 12-miRNA signature we were able to differentiate between AD and controls with an accuracy of 93.3%, a specificity of 95.1%, and a sensitivity of 91.5%. The differentiation of AD from other neurological diseases was possible with accuracies between 73.8% and 77.8%. The differentiation of the other CNS disorders from controls yielded even higher accuracies. Overall design: Examination of the miRNA profile in blood samples of 48 AD patients and 22 controls

Publication Title

A blood based 12-miRNA signature of Alzheimer disease patients.

Alternate Accession IDs

GSE46579

Sample Metadata Fields

Sex, Age, Subject

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accession-icon GSE75824
Expression data from pam48 (mterf6-1) mutants
  • organism-icon Arabidopsis thaliana
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Of the members of mitochondrial transcription termination factors (mTERFs) found in metazoans and plants known to regulate organellar gene expression at various levels, plant mTERF6 promotes maturation of a tRNA

Publication Title

Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.

Alternate Accession IDs

E-GEOD-75824

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP173260
Functional relationship of GUN1 and FUG1 in plastid proteostasis
  • organism-icon Arabidopsis thaliana
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

GUN1 integrates retrograde signals in the chloroplast but the underlying mechanism is elusive. FUG1, a chloroplast translation initiation factor, and GUN1 are co-expressed at the transcript level, and FUG1 co-immunoprecipitates with GUN1. We used mutants of GUN1 (gun1-103) and FUG1 (fug1-3) to analyse their functional relationship at the physiological and systems-wide level, the latter including transcriptome and proteome analyses. Absence of GUN1 aggravates the effects of decreased FUG1 levels on chloroplast protein translation, resulting in transient additive phenotypes with respect to photosynthesis, leaf coloration, growth and cold acclimation. Variegation of the var2 mutant is enhanced by gun1-103 in terms of increasing the fraction of white sectors, in contrast to fug1-3 that acts as suppressor. The transcriptomes of fug1-3 and gun1-103 are very similar, but absence of GUN1 alone has almost no effects on protein levels, whereas chloroplast protein accumulation is markedly decreased in fug1-3. In gun1 fug1 double mutants, effects on transcriptomes and particularly proteomes are enhanced. Our results show that GUN1 function becomes critical when chloroplast proteostasis is perturbed by decreased translation (fug1) or degradation (var2) of chloroplast proteins. The functions of FUG1 and GUN1 appear to be related, corroborating the view that GUN1 operates in chloroplast proteostasis. Overall design: Examination of differential gene expression in the Arabdidopsis thaliana gun1, fug1 and gun1 fug1 mutants compared to wild type in three replicates

Publication Title

Relationship of GUN1 to FUG1 in chloroplast protein homeostasis.

Alternate Accession IDs

GSE123583

Sample Metadata Fields

Subject

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accession-icon GSE54573
Identification of target genes of translation-dependent signalling in Arabidopsis
  • organism-icon Arabidopsis thaliana
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Changes ins organellar gene expression trigger retrograde signalling. Prolyl-tRNA synthetase (PRORS1) is located in chloroplasts and mitochondria. Thus, prors1-2 mutants are impaired in chloroplast and mitochondrial gene expression.

Publication Title

Identification of target genes and transcription factors implicated in translation-dependent retrograde signaling in Arabidopsis.

Alternate Accession IDs

E-GEOD-54573

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE94521
Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration
  • organism-icon Homo sapiens
  • sample-icon 57 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

The in vitro test battery of the European research consortium ESNATS (novel stem cell-based test systems) has been used to screen for potential human developmental toxicants. As part of this effort, the migration of neural crest (MINC) assay has been used to evaluate chemical effects on neural crest function. It identified some drug-like compounds in addition to known environmental toxicants. The hits included the HSP90 inhibitor geldanamycin, the chemotherapeutic arsenic trioxide, the flame-retardant PBDE-99, the pesticide triadimefon and the histone deacetylase inhibitors valproic acid and trichostatin A. Transcriptome changes triggered by these substances in human neural crest cells were recorded and analysed here to answer three questions: (1) can toxicants be individually identified based on their transcript profile; (2) how can the toxicity pattern reflected by transcript changes be compacted/ dimensionality-reduced for practical regulatory use; (3) how can a reduced set of biomarkers be selected for large-scale follow up? Transcript profiling allowed clear separation of different toxicants and the identification of toxicant types in a blinded test study. We also developed a diagrammatic system to visualize and compare toxicity patterns of a group of chemicals by giving a quantitative overview of altered superordinate biological processes (e.g. activation of KEGG pathways or overrepresentation of gene ontology terms). The transcript data were mined for potential markers of toxicity, and 39 transcripts were selected to either indicate general developmental toxicity or distinguish compounds with different modes-of-action in read-across. In summary, we found inclusion of transcriptome data to largely increase the information from the MINC phenotypic test.

Publication Title

Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration.

Alternate Accession IDs

E-GEOD-94521

Sample Metadata Fields

Sex, Specimen part

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accession-icon E-MTAB-375
Transcription profiling by array of Arabidopsis after exposure to different temperatures and light levels
  • organism-icon Arabidopsis thaliana
  • sample-icon 175 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

High-density kinetic analysis of the metabolomic and transcriptomic response of Arabidopsis to temperature and light

Publication Title

High-density kinetic analysis of the metabolomic and transcriptomic response of Arabidopsis to eight environmental conditions.

Alternate Accession IDs

None

Sample Metadata Fields

Specimen part, Time

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accession-icon E-MTAB-1344
Transcription profiling by array of Arabidopsis thaliana Col-0 and RAP2.4a mutants under time dependent light stress by transfer to high light
  • organism-icon Arabidopsis thaliana
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Comparison of expression of Arabidopsis thaliana Col-0 and T-DNA insertion line of RAP2.4a under time dependent light stress by transfer to high light

Publication Title

Meta-analysis of retrograde signaling in Arabidopsis thaliana reveals a core module of genes embedded in complex cellular signaling networks.

Alternate Accession IDs

None

Sample Metadata Fields

Specimen part

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accession-icon GSE65168
Cellular and molecular characterization of the altered metabolism in RCC
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

RCC cells (786-O) were transfected with VHL. The parental cell line should be compared to the transfectant (+VHL) under nomoxia as well as under hypoxia conditions.

Publication Title

Distinct von Hippel-Lindau gene and hypoxia-regulated alterations in gene and protein expression patterns of renal cell carcinoma and their effects on metabolism.

Alternate Accession IDs

E-GEOD-65168

Sample Metadata Fields

Cell line

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accession-icon GSE75582
Stem cell-derived immature human dorsal root ganglia neurons to identify peripheral neurotoxicants
  • organism-icon Homo sapiens
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Safety sciences and the identification chemical hazard have been seen as one of the most immediate practical applications of human pluripotent stem cell technology. Protocols for the generation of many desirable human cell types have been developed, but optimization of neuronal models for toxicological use has been astonishingly slow, and the wide, clinically- important field of peripheral neurotoxicity is still largely unexplored. Here, a 2-step protocol to generate large lots of identical peripheral human neuronal precursors was characterized and adapted to the measurement of peripheral neurotoxicity. High content imaging allowed an unbiased assessment of cell morphology and viability. The computational quantification of neurite growth as functional parameter highly sensitive to disturbances by toxicants was used as endpoint reflecting specific neurotoxicity. The differentiation of cells towards dorsal root ganglia neurons was tracked in relation to a large background data set based on gene expression microarrays. On this basis, a peripheral neurotoxicity (PeriTox) test was developed as first toxicological assay that harnesses the potential of human pluripotent stem cells to generate cell types/tissues that are not otherwise available for prediction of human systemic organ toxicity. Testing of more than 30 chemicals showed that human neurotoxicants, as well as neurite growth enhancers, were correctly identified. Various classes of chemotherapeutics causing human peripheral neuropathies were identified, while they were missed when tested on human central neurons. The PeriTox-test established here shows the potential of human stem cells for clinically-relevant safety testing of drugs in use and of new emerging candidates.

Publication Title

Stem Cell-Derived Immature Human Dorsal Root Ganglia Neurons to Identify Peripheral Neurotoxicants.

Alternate Accession IDs

E-GEOD-75582

Sample Metadata Fields

Sex, Specimen part, Cell line

View Samples
...

refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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